The mycotoxin T-2 inhibits hepatic cytochrome P4503A activity in pigs

Mycotoxins are toxic metabolites produced by fungi that readily colonize crops. After ingestion, these mycotoxins can compromise intestinal health, and once entering the blood stream, even affect the liver and its metabolizing enzymes. It was therefore the aim of the present study to investigate the effect of T-2 toxin, an emerging and potent Fusarium mycotoxin, on the enzymatic activity of cytochrome P4503A (CYP3A) metabolizing enzymes in the liver of pigs. In addition, a yeast-derived feed additive that claims to bind T-2 toxin was included in the study to evaluate its efficacy. Our results demonstrated that a 14-days intake of T-2 toxin contaminated feed at a dose of 903 μg/kg feed, whether or not combined with the mycotoxin binder, results in a substantial inhibition of the CYP3A activity in the liver of pigs. This result may be of importance for animal health, the pharmacokinetics and the withdrawal time of drugs that are substrate of CYP3A enzymes, and consequently can be a threat for public health with respect to tissue residues of these drugs.     

The immunogenicity in healthy infants and efficiency to prevent mother to child transmission of Hepatitis B virus of a 10 μg recombinant yeast-derived Hepatitis B vaccine (Hep-KSC)

Background and AimsTo evaluate immunogenicity and efficacy of a 10 μg recombinant Saccharomyces cerevisiae-derived hepatitis B vaccine (Kangtai Biological Products Co. Ltd, Shenzhen, China) (Hep-KSC) in newborns.MethodsOverall 1197 infants born to mothers negative for HBV markers (NM group) and 534 born to HBsAg-positive mothers (PM Group) were enrolled. Infants in NM group were given 10 μg Hep-KSC, 10 μg Engerix-B or 5 μg Hep-KSC and those in PM group received 10 μg Hep-KSC or 10 μg Engerix-B at 0, 1 and 6 months, with an additional 200 IU HBIG at birth for the latter.ResultsFor NM Group, 10 μg Hep-KSC paralleled 10 μg Engerix-B but outperformed 5 μg Hep-KSC regarding seroprotective rate (95.06% vs 94.83% vs 89.67%, p = 0.0077) and anti-HBs geometric mean concentration (GMC) (798.87 mIU/ml vs 790.16 mIU/ml vs 242.04 mIU/ml, p < 0.0001) at 7 months. The proportion of infants with anti-HBs greater than 1000 mIU/ml was higher in 10 μg Hep-KSC than 5 μg Hep-KSC group (45.77% vs 11.93%, p < 0.0001) at 7 and 12 months. For PM Group, the HBsAg positivity rate in 10 μg Hep-KSC and 10 μg Engerix-B group was 1.60% and 4.27% at 7 months, respectively. In 10 μg Hep-KSC group, 93.61% and 91.29% achieved seroprotection at 7 and 12 months, respectively, and correspondingly 90.24% and 86.96% in 10 μg Engerix-B group. The anti-HBs GMC was comparable between 10 μg Hep-KSC and 10 μg Engerix-B group at 7 and 12 months (575.31 mIU/ml vs 559.64 mIU/ml; 265.79 mIU/ml vs 264.48 mIU/ml).Conclusions10 μg Hep-KSC might be appropriate for neonatal immunization with good immunogenicity and efficacy, especially for infants born to HBsAg-positive mothers.     

HBIG联合国产、进口重组乙型肝炎疫苗阻断乙型肝炎母婴传播的效果观察

目的了解乙肝免疫球旦白（HBIG）分别联合相同剂量国产、进口重组（酵母）乙肝疫苗阻断乙肝病毒（HBV）母婴传播的效果。方法用HBIG分别联合国产、进口乙肝疫苗10μg／0．5mL免疫乙肝病毒表面抗原（HBsAg）、乙肝病毒膜抗原（HBeAg）双阳性或只有HBsAg阳性母亲的新生儿共130例,采用0、1、6个月接种程序,测定乙肝病毒表面抗体（抗-HBS）滴度及HBsAg。结果国产组新生儿HBsAg阳性率为1．49％,保护率为98．14％;进口组新生儿HBsAg阳性率4．76％,保护率为94．05％。两组间比较差异无统计学意义（P〉0．05）。结论HBIG联合国产、进口10μg乙型肝炎重组（酵母）疫苗阻断乙肝母婴传播的效果同样良好。     

重组乙型肝炎疫苗(酵母)免疫后10年的抗体持久性及免疫记忆观察

目的观察重组乙型肝炎(乙肝)疫苗(酵母)(YDV)免疫后10年的抗体持久性及免疫记忆。方法追踪观察按照免疫程序全程免疫后10年儿童的乙肝病毒表面抗体(抗-HBs)持久性;分别对免疫后5年和10年抗-HBs阴转的儿童,加强免疫YDV 1剂,观察其免疫记忆反应。结果抗-HBs阳性率、有效阳性率、几何平均滴度逐年下降,分别由免疫后1年的92.08%、84.16%、29.21mIU/ml降至10年后的65.17%、40.45%、5.38mIU/ml;年均递减率分别为3.76%、7.82%、17.14%。抗-HBs阳性率下降速率较慢,而有效阳性率则较快,并随免疫时间的延长,各项指标的年均递减率逐年降低,推测免疫的低阳性率水平可能维持较长时间。结论YDV免疫后存在较好的免疫记忆,免疫后10年无需加强免疫。     

重组乙型肝炎疫苗(酵母)免疫的保护效果及成本-效益评价

目的评价重组乙型肝炎(乙肝)疫苗(酵母)(YDV)免疫的保护效果及成本-效益。方法在同龄儿童中设免疫组和未免疫组,对照研究免疫与未免疫儿童组乙肝病毒表面抗原(HBsAg)携带率之差异及其免疫的保护效果。同时,以本研究免疫组的HBsAg携带率与实施乙肝疫苗免疫策略前山西省同龄组儿童的HBsAg携带率做对比,分析YDV的保护效果,并进行免疫的成本-效益分析。结果免疫组的HBsAg携带率为0.41%,无免疫史组的携带率为3.24%,差异有非常显著的统计学意义;两组对比分析的疫苗保护率为87.35%。实施免疫策略前后同龄组儿童HBsAg携带率比较计算的疫苗保护率为95.00%。分别按全国和山西省的乙肝病毒(HBV)感染本底资料分析免疫的成本-效益表明,每接种1 000人份YDV可分别减少106名和103名HBsAg慢性携带者,27名和26名慢性肝病患者,粗略估算直接的成本-效益之比为1∶27。结论YDV免疫的保护效果良好,并有非常好的成本-效益。     

国产重组(酵母)乙型肝炎疫苗免疫效果观察

为研究和比较国产重组(酵母)乙型肝炎(乙肝)疫苗与血源乙肝疫苗的免疫效果,采用单纯随机方法,于免疫后1年对重组(酵母)乙肝疫苗接种的新生儿进行随访观察,采血检测乙肝病毒表面抗原(HBsAg)、乙肝病毒表面抗体(抗-HBs)、乙肝病毒核心抗体(抗-HBc).HBsAg阳性母亲所生的儿童其HBsAg阳性率为5.2%(4/77),抗-HBs阳性率为83.3%(65/78),疫苗保护效果为91.3%;HBsAg阴性母亲所生的儿童其HBsAg阳性率为0.9%(1/114),抗-HBs阳性率为97.4%(111/114),疫苗保护效果为79.5%.重组(酵母)乙肝疫苗有较好的近期保护效果和免疫原性,与以前使用的血源乙肝疫苗相当.     

Saccharomyces cerevisiae-derived virus-like particle parvovirus B19 vaccine elicits binding and neutralizing antibodies in a mouse model for sickle cell disease

Parvovirus B19 infections are typically mild in healthy individuals, but can be life threatening in individuals with sickle cell disease (SCD). A Saccharomyces cerevisiae-derived B19 VLP vaccine, now in pre-clinical development, is immunogenic in wild type mice when administered with the adjuvant MF59. Because SCD alters the immune response, we evaluated the efficacy of this vaccine in a mouse model for SCD. Vaccinated mice with SCD demonstrated similar binding and neutralizing antibody responses to those of heterozygous littermate controls following a prime-boost-boost regimen. Due to the lack of a mouse parvovirus B19 challenge model, we employed a natural mouse pathogen, Sendai virus, to evaluate SCD respiratory tract responses to infection. Normal mucosal and systemic antibody responses were observed in these mice. Results demonstrate that mice with SCD can respond to a VLP vaccine and to a respiratory virus challenge, encouraging rapid development of the B19 vaccine for patients with SCD.     

Efficacy of yeast-derived recombinant hepatitis B vaccine after being used for 12 years in highly endemic areas in China

Objective

To evaluate the long-term efficacy and duration of yeast-derived recombinant hepatitis B vaccine in hepatitis B virus (HBV)-endemic areas.

Method

A cross-sectional investigation was carried out in five HBV-endemic areas. Children who were born between 1997 and 2008 and vaccinated with yeast-derived recombinant hepatitis B vaccine were selected. Serum samples were taken to test HBV infection markers by microparticle enzyme immunoassay, and the results were compared to those before vaccination.

Results

7066 subjects were enrolled. The average adjusted hepatitis B surface antigen (HBsAg) prevalence was 1.02%. HBV core antibody (anti-HBc) prevalence was 3.54%. The overall percentage of HBsAg(−)&Anti-HBc(−)&Anti-HBs(+) was 61.34%. With time after immunization, the percentage annually decreases from 86.11% in 2008 to 49.80% in 1997. Geometric mean concentration (GMC) of anti-HBs decreased significantly annually. The portion of GMC = 100–999.9 mIU/ml was 48.0% in 2008, and decreased to 16.7% in 1997.

Conclusion

HBsAg prevalence decreased dramatically. This shows that the yeast-derived recombinant hepatitis B vaccine is effective and stable after being used for 12 years in HBV-endemic areas. It is not suggested to carry out booster immunization.     

重组酵母乙型肝炎疫苗血清学免疫效果的观察

目的：探讨国产重组酵母乙型肝炎（乙肝）疫苗不同剂量，不同间隔时间免疫后4年的血清学免疫效果。方法：对乙肝表面抗原（HBsAg)阳性母亲和阴性母亲的新生儿，按第1针分别接种10μg或5μg乙肝疫苗，4年后观察免疫效果，同时对HBsAg阴性母亲的新生儿选择第3针与第1针的不同间隔时间进行接种，全程免疫后4年观察免疫效果。结果：乙肝疫苗全程免疫4年后，HBsAg阳性母亲的新生儿第1针接种10μg组抗－HBs阳性率高于5μg组，差别有显著性，对HB－sAg阴性母亲的新生儿进行免疫时，乙肝疫苗第3针与第1针间隔5，6，8个月，其抗－HBs阳性率及抗体水平，差别均无显著性，所有接种对象，全程免疫4年后抗－HBs阳性率及抗体水平均较低。结论：HBsAg阳性母亲的新生儿国产重组酵母乙肝疫苗第1针10μg组全程免疫效果优于5μg组，HBsAg阴性母亲的新生儿乙肝疫苗第3针与第1针间隔5，6，8个月都是可行的，4周岁儿童乙肝疫苗加强接种是必要的。     

Monitoring the efficacy of infant hepatitis B vaccination and revaccination in 0- to 8-year-old children: Protective anti-HBs levels and cellular immune responses

Vaccination against hepatitis B virus (HBV) is recommended worldwide. The aim of this study was to assess the efficacy of infant hepatitis B vaccination and revaccination in 0- to 8-year-old children in the context of protective anti-HBs levels and cellular immune responses. Using a random questionnaire survey, 1695 pre-school children were recruited as research subjects during January 2015 to June 2017. Blood samples were obtained to measure HBV serological markers as well as peripheral immunocytes. The children were divided into non-, low- and hyper- responsive groups (NR, LR, and HR) based on the vaccination efficacy. Additionally, the effect of revaccination on the NR group was evaluated at 1 month after completion of the vaccination course. Among a total of 1695 children, 1591 (93.86%) were infants who were followed while undergoing their primary course of hepatitis B vaccination at the 0-1-6 month schedule, and 1249 (79.30%) of them developed antibodies against HBsAg (anti-HBs) titers greater than 10 IU/L. The results of immunocyte studies indicated that the CD8⁺ T cells, CD4⁺CD45RO⁺ T cells, CD8⁺CD45RA⁺ T cells, and T follicular helper (Tfh) cells increased significantly in NR compared with HR. However, lymphocytes, CD4⁺ T cells, and CD4⁺CD45RA⁺ T cells in NR were lower than that in HR. 96 of the non-response cases showed seroprotection after revaccination among 103 cases. Therefore, most of the preschool children who received hepatitis B vaccine in infancy achieved significant seroprotection. Seroconversion rates of individuals revaccinated after initial vaccination failure were significantly higher than those after primary vaccination. Different vaccination efficacy groups showed significant changes in circulating immunocytes, which might be a factor affecting the recombinant HBV vaccine’s immune effectiveness.